Effects of a Step-Therapy Program for Angiotensin Receptor Blockers on Antihypertensive Medication Utilization Patterns and Cost of Drug Therapy

BACKGROUND: Step therapy for angiotensin receptor blockers (ARBs)requiring prior use of angiotensin-converting enzyme inhibitors (ACEIs) is a common cost-containment intervention in managed care. OBJECTIVES: This study was designed to assess the effectiveness of the step-therapy intervention for ARBs, including ARB/hydrochlorthiazide (HCTZ)combinations, as measured by prescription use patterns and antihypertensive drug ingredient costs. METHODS: Rejected and paid pharmacy claims data were evaluated from 3 health plans with a total membership of approximately 1 million. These plans had implemented a step-therapy intervention for ARBs from May 1,2001, through February 28, 2003. Patients in the intervention group who had experienced a claim rejection for an ARB within the first 6 months of program implementation (i.e., had had no ACEI [or ACEI/HCTZ combination/or ARB [or ARB/HCTZ] claim in the preceding 3 months) were followed for 1 year after the ARB claim rejection. The rate of initiation of ARB versus ACEI and other outcomes was compared with similar data from a health plan with approximately 2 million members that did not have a step therapy intervention for ARBs (comparison group). Mean and median total antihypertensive drug ingredient costs per patient and per day of therapy over 12 months were analyzed for the intervention and comparison groups. One pharmacy benefit manager administered the pharmacy benefits for the intervention and comparison health plans during the entire study period fromMay 1, 2001, through February 28, 2004, and the drug formulary was similar for all health plans. RESULTS: In the step-therapy health plans, before the criterion for 15 months of continuous eligibility was applied, there were 8,904 patients (approximately 0.9% of health plan members) who either attempted and were rejected for an ARB or who newly started ACEI therapy, compared with 44,788 patients (approximately 2.2% of members in the comparison health plan) who newly started ARB or ACEI therapy without the step-therapy intervention. After the eligibility criterion was applied, there were 6,758 intervention health plan members (0.7% of members) and 33,709 comparison health plan members (1.7% of members) in the 2 study groups. In addition to the smaller proportion of total members affected by the intervention in the ARB step-therapy health plans, a smaller proportion of ARB/ACEI patients attempted to obtain an ARB antihypertensive drug cost per patient was lower in the intervention group($370.00) than in the comparison group ($445.12; P less than 0.001), and the average cost per day of antihypertensive drug therapy was 12.8% lower in the step therapy group ($0.82) than in the comparison group ($0.94). Unadjusted annual cost savings were $75.12 per patient, and ordinary least squares regression analysis showed that the ARB step-therapy intervention was associated with $43.91 in antihypertensive drug cost savings per patient over 12 months. CONCLUSIONS: Within 12 months of follow-up, a step-therapy intervention forARBs was associated with an 18% ratio of ARB users to total ACEI/ARB users compared with a 31% ratio in a comparison health plan without the ARB step-therapy intervention. Approximately 45% of patients who did not receive an ARB as a result of the step-therapy intervention had either switched to or added an ARB within 12 months of the intervention, and almost 7% of patients did not receive any antihypertensive therapy. Antihypertensive drug cost was about 13% lower for the ACEI/ARB patients in the intervention group,creating approximately $368,000 in savings in 1 year or $0.03 per member per month across the 1 million health plan members.

METHoDS: Rejected and paid pharmacy claims data were evaluated from 3 health plans with a total membership of approximately 1 million. These plans had implemented a step-therapy intervention for ARBs from May 1, 2001, through February 28, 2003. Patients in the intervention group who had experienced a claim rejection for an ARB within the first 6 months of program implementation (i.e., had had no ACEI [or ACEI/HCTZ combination] or ARB [or ARB/HCTZ] claim in the preceding 3 months) were followed for 1 year after the ARB claim rejection. The rate of initiation of ARB versus ACEI and other outcomes was compared with similar data from a health plan with approximately 2 million members that did not have a steptherapy intervention for ARBs (comparison group). Mean and median total antihypertensive drug ingredient costs per patient and per day of therapy over 12 months were analyzed for the intervention and comparison groups. one pharmacy benefit manager administered the pharmacy benefits for the intervention and comparison health plans during the entire study period from May 1, 2001, through February 28, 2004, and the drug formulary was similar for all health plans.
RESUlTS: In the step-therapy health plans, before the criterion for 15 months of continuous eligibility was applied, there were 8,904 patients (approximately 0.9% of health plan members) who either attempted and were rejected for an ARB or who newly started ACEI therapy, compared with 44,788 patients (approximately 2.2% of members in the comparison health plan) who newly started ARB or ACEI therapy without the step-therapy intervention. After the eligibility criterion was applied, there were 6,758 intervention health plan members (0.7% of members) and 33,709 comparison health plan members (1.7% of members) in the 2 study groups. In addition to the smaller proportion of total members affected by the intervention in the ARB step-therapy health plans, a smaller proportion of ARB/ACEI patients attempted to obtain an ARB (1,296/6,758 or 19.2%) compared with the health plan without step therapy (8,697/33,709 or 25.8%, P <0.001). of the 1,296 patients who attempted to obtain an ARB and were rejected in the step-therapy group, 578 patients (44.6%) went through the prior-authorization process and received an ARB as initial therapy, 632 patients (48.8%) received other antihypertensive therapy, and 86 patients (6.6%) did not receive any antihypertensive therapy within the 12-month follow-up period. In the 12 months of follow-up, 51.1% (323/632) of patients in the intervention group who received other antihypertensives as index therapy switched to or added an ARB, and 1,234 of total ACE/ARB patients (n = 6,758, 18.3%) received ARB therapy in the health plan with step therapy compared with 10,498 of 33,709 total ACEI/ARB patients (31.1%) who received ARB therapy in the health plan without step therapy. The mean antihypertensive drug cost per patient was lower in the intervention group ($370.00) than in the comparison group ($445.12; P <0.001), and the average cost per day of antihypertensive drug therapy was 12.8% lower in the steptherapy group ($0.82) than in the comparison group ($0.94). Unadjusted annual cost savings were $75.12 per patient, and ordinary least squares regression analysis showed that the ARB step-therapy intervention was associated with $43.91 in antihypertensive drug cost savings per patient over 12 months.
ConClUSIonS: Within 12 months of follow-up, a step-therapy intervention for ARBs was associated with an 18% ratio of ARB users to total ACEI/ARB users compared with a 31% ratio in a comparison health plan without the ARB step-therapy intervention. Approximately 45% of patients who did not receive an ARB as a result of the step-therapy intervention had either switched to or added an ARB within 12 months of the intervention, and almost 7% of patients did not receive any antihypertensive therapy. Antihypertensive drug cost was about 13% lower for the ACEI/ARB patients in the intervention group, creating approximately $368,000 in savings in 1 year or $0.03 per member per month across the 1 million health plan members. T he clinical benefits of angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) in the treatment of hypertension have been well established. [1][2][3] Because of the clinical efficacy and safety of these drugs, ARBs and ACEIs are recommended in the Seventh Report of the Joint National Committee on Prevention, Detection,

Effects of a Step-Therapy Program for Angiotensin Receptor Blockers on Antihypertensive Medication Utilitzation Patterns and Cost of Drug Therapy
A step-therapy intervention can be implemented using an automated concurrent claim review process in which the pharmacy benefits manager (PBM) searches its drug claims history for evidence of prior use of the required steptherapy drug. 8 Alternatively, a step-therapy intervention can involve a manual process with review of the patient' s drug use history after the claim rejection. In the case of automated concurrent claim review ("smart edit") for an ARB step-therapy intervention, an ARB claim (including an ARB in combination with hydrochlorothiazide [HCTZ]) would be approved only with previous history of use of an ACEI (including an ACEI in combination with HCTZ) or if the patient had previously received an ARB. In most cases, when the patient is unable to get the ARB medication, the pharmacist will contact the prescriber to obtain a verbal order for an alternative medication.
Prior experience with step therapy in other disease states suggests that more than 50% of patients prescribed cyclooxygenase-2 (COX-2) inhibitor therapy did not attempt a PA following a point-of-care pharmacy claim rejection. 9 Another study found that up to 70% of patients did not attempt to obtain a PA after their pharmacy claim for a COX-2 was denied. 10 Several studies have been conducted to determine the effect of PA on health outcomes, focusing on direct costs and health care resource use among those affected by a PA. [11][12][13] However, little is known about the antihypertensive drug use patterns of members when a step-therapy program is in place for ARBs.
This study was designed to evaluate the hypertensionrelated pharmacy use and costs for 3 managed care plans that implemented an ARB step-therapy intervention compared with 1 health plan with no ARB step-therapy intervention. The steptherapy intervention employed a "smart edit" in which each new claim for an ARB triggered an electronic search of the patient' s pharmacy claim history for either an ACEI, including an ACEI/ HCTZ, or an ARB, including an ARB/HCTZ, in the preceding 3-month period. The ARB claim was rejected if there was no prior use of these drugs and the pharmacist or patient had to contact the prescriber to obtain either an alternative to the ARB or a PA (e.g., the patient had attempted an ACEI claim previously that was not in the pharmacy claims history).
Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines. 4 However, with the availability of generic ACEIs and the relatively higher cost of the ARBs, some managed care plans have implemented cost-containment strategies, including preference for ACEI therapy to ARBs.
Managed care organizations are increasing adopting interventions such as step-therapy requirements and priorauthorization (PA) programs to contain costs while attempting to improve patient care.
Step-therapy criteria are widely adopted by managed care plans to guide appropriate medication use and manage the cost of more expensive therapy. 5 In 2005, nearly 80% of commercial plans and 64% of Medicare Advantage plans reported using step-care protocols or treatment guidelines. Additionally, in 2005, 96% of commercial plans and 73% of Medicare Advantage health plans reported managing the prescribing of drugs outside of formularies via PA. 6 A survey conducted in 2004 of 404 employers representing 8.6 million members found that the use of step-therapy edits increased from 22% of employers in 2000 to 28% in 2002 and 45% in 2004. 7

Approximate
Step-Therapy  Effects of a Step-Therapy Program for Angiotensin Receptor Blockers on Antihypertensive Medication Utilitzation Patterns and Cost of Drug Therapy nn Methods Study Design and Data Source A retrospective cohort study was designed to assess the impact of an ARB step-therapy intervention on use of antihypertensive agents during a 12-month follow-up period. The intervention group included members from 3 health plans in which pharmacy benefits were managed by a PBM and where an ARB step-therapy program was in place between May 1, 2001, and February 28, 2003 ( Table 1). The 3 health plans were commercial managed care plans located in the Northeast and Midwest. Membership in the 3 plans ranged from 150,000 to 500,000 patients.

Description of Health Plans With and Without ARB Step Therapy
A comparison group of members was selected from 1 commercial managed care health plan in the West without ARB step therapy in 2002 or 2003 and with average membership of 2 million. All health plans had a mix of 2-tier and 3-tier pharmacy benefit plan designs with similar average copayments for 3-tier business ( Table 2). The drug formulary included 7 generic ACEIs and ACEI/HCTZ products (captopril, enalapril, fosinopril, lisinopril, captopril/HCTZ, enalapril/HCTZ, and lisinopril/HCTZ). Seven of 21 available brand ACEI and ACEI/ HCTZ products and 6 of 12 brand ARB and ARB/HCTZ products were on the drug formulary. Mail order was available in all health plans, and members were allowed to fill prescriptions for up to a 3-month (90-day) supply. In general, the ratio of mail order to community pharmacy was no more than 5% to 6% of total prescriptions dispensed.
All rejected and paid pharmacy claims data for ARBs, ARB/ HCTZ combinations, ACEIs, and ACEI/HCTZ combinations were extracted using the Generic Product Identifier code (Medi-Span classification system). For simplification, future references to ARBs or ACEIs in this article include ARB/HCTZ combinations and ACEI/HCTZ combinations.
Patients in the intervention group who had encountered a claim reject for an ARB or had had a paid claim for an ACEI over the 6-month identification period and had no ARB or ACEI claim in the previous 3 months (new starts) were followed for 1 year. The patient identification period in the intervention health plans was May 1, 2001, through February 28, 2003, based on the initiation of the step-therapy intervention for each plan (Table 1). Patients in the comparison health plan who were newly started on an ACEI or ARB during a 6-month selection period were identified from paid claims data with dates of service from September 1, 2002, through February 28, 2003 ( Figure 2). The index date was defined as the date of the first attempt to obtain an ARB (intervention group) or the initial fill date for an ARB (comparison group) or ACEI (intervention or comparison groups). Combination treatment was defined as having claims for another antihypertensive drug on the index date or in the previous 3 months with overlapping days supply. New start patients were included in the study if they were aged ≥18 years on the index date and were continuously enrolled for the 3-month preindex and 12-month follow-up periods ( Figures 1 and 2).

Outcome Measures
The outcome measures for the group with step therapy versus the comparison group without step therapy included the rate of initiation on an ACEI or ARB and the proportion of patients who attempted to receive an ARB (and had had no ARB or ACEI claim in the previous 3 months in the step-therapy group) or who were newly started on an ARB. The type of initial antihypertensive therapy received by patients in the intervention group following the ARB claim reject was also evaluated. The initial therapy in the step-therapy group was identified as the first paid claim for an antihypertensive drug following the rejected claim during the 12-month follow-up period. Additionally, the proportion of patients in the intervention group who received other

FIGURE 1
* initial therapy is the first antihypertensive drug therapy the patient received following the rejected arB claim in the 12-month follow-up period or the first therapy for the patients who newly started on an aCei (including HCtZ combinations). aCei = angiotensin-converting enzyme inhibitor; arB = angiotensin receptor blocker; HCtZ = hydrochlorothiazide; HtN = hypertensive.
Step-Therapy Group: Members in Health Plans Where a Step-Therapy Program Was Implemented (N = 1,000,000)

Effects of a Step-Therapy Program for Angiotensin Receptor Blockers on Antihypertensive Medication Utilitzation Patterns and Cost of Drug Therapy
Ordinary least squares regression analysis was used to estimate the impact of the step-therapy edit on total antihypertensive drug costs during the 12-month period while controlling for potential confounding variables, such as age, gender, Chronic Disease Score (CDS), average copay per claim, and number of 30-day antihypertensive drug claims. Model diagnostics were performed, including tests for multicollinearity.
A CDS was determined for patients in the current study using the method by Clark et al. for pharmacy claims use from the 6 months before each patient' s index date to identify chronic diseases (i.e., coronary and peripheral vascular disease, hypertension, hyperlipidemia, congestive heart failure, asthma, and diabetes mellitus). 14 Total cost weight was used as a severity measure and estimate of the patient' s total chronic disease burden. nn

Results
In the health plans with the step-therapy intervention for ARBs before application of the criterion for 15 months of continuous eligibility, there were 8,904 patients (approximately 0.9% of health plan members) who either attempted and were rejected for an ARB or who newly started ACEI therapy ( Figure 1) compared with 44,788 patients (approximately 2.2% of members in the comparison health plan) who newly started ARB or ACEI therapy without the step-therapy intervention ( Figure 2). After the criterion of 15 continuous months of eligibility was applied, 6,758 of health plan members (0.7%) were affected by the ARB step-therapy intervention versus 33,709 health plan members (1.7%) who initiated either ACEI or ARB therapy in the comparison group.
Of the 6,758 patients who met the eligibility criteria and either newly started (i.e., no ACEI or ARB in the 3-month preindex period) an ACEI or attempted to obtain an ARB in the intervention group, the mean age (52.9 years) was lower than the comparison group (n = 33,709), which had a mean age of 57.6 years ( Table 3). The gender ratio between the intervention group (54.0% male) and the comparison group (54.4% male) was similar. The mean CDS for the intervention group (1598.30) was lower than for the comparison group (1860.95).

Rate of Initiation
Approximately 19.2% (1,296 of 6,758) of patients in the steptherapy group attempted to get an ARB compared with 25.8% (8,697 of 33,709) in the comparison group who started an ARB (Figures 1 and 2). Of the 1,296 patients who attempted to obtain an ARB under the step-therapy intervention, 44.6% received an ARB as initial therapy (via PA from the prescriber), 48.8% received other antihypertensive therapy, and 6.6% did not receive any antihypertensive therapy within 12 months of the index date (Table 4). Among the patients who attempted to get an ARB as initial therapy, a significantly greater proportion of the intervention group used antihypertensive monotherapy than did the comparison group, 50.7% versus 38.4%, respectively antihypertensive therapy following the rejected ARB claim, but who were switched to or added ARB therapy within 3, 6, and 12 months, was determined.
Other outcome measures for the step-therapy group versus the comparison group included antihypertensive drug use and antihypertensive drug acquisition costs. The mean and median number of claims, number of unique drugs, and days supply received were computed as well as antihypertensive ingredient cost per patient and per day of antihypertensive drug therapy over the 12-month follow-up period. Ingredient cost reported in this study is the allowed drug cost before subtraction of member cost share (copayment or coinsurance) or manufacturer rebates.

Statistics
All statistical and descriptive analyses were performed using SPSS version 14.0 for Windows (Chicago, Illinois). Mean and standard deviations were calculated for continuous variables. Chi-square test and Student' s t test were computed to test the differences between groups, and a value of P <0.05 was established as a statistically significant difference. Mean, median, and 95% confidence intervals were calculated for pharmacy cost and use.

Pharmacy Use and Costs
Pharmacy use, unique medications, days supply, and antihypertensive drug ingredient costs were examined in the step-therapy and comparison groups as well as in the subgroup of patients who attempted or were started on an ARB. Mean antihypertensive drug ingredient costs per patient were lower in the steptherapy group than in the comparison group despite a similar number of pharmacy claims per member, number of unique drugs per member, and days supply received ( Table 6). The mean 12-month antihypertensive drug costs per patient were 16.9% lower for the step-therapy group ($370.00) than for the comparison group ($445.12, P <0.001). The mean ingredient cost per day was 12.8% lower for the step-therapy group overall for ACEI and ARB patients ($0.82) than for the comparison group ($0.94, P <0.05) and 35.9% lower than the mean cost per day ($1.28) for the 578 patients in the step-therapy group who attempted and received an ARB.
Ordinary least squares regression analysis showed that the edit was associated with a $43.91 ingredient cost savings per patient over 12 months (Table 7). Applying the $0.12 savings in direct ingredient cost per day of antihypertensive drug therapy to 3,067,351 days of drug therapy for the 6,758 patients in the step-therapy group yields 1-year drug cost savings of $368,082. For this health plan with approximately 1 million members, the drug cost savings per member per month (PMPM) associated with this ARB step-therapy intervention were at least $0.03.

nn Discussion
As pharmacy use per member continues to increase, there is a need for managed care plans to develop and implement successful cost-containment mechanisms. One of the primary goals of step-therapy programs is to promote lower-cost drugs for the majority of members and to promote cost-effective use of more expensive, newer therapies. An ARB step-therapy program was shown to reduce the number of patients receiving an ARB as initial therapy, delay the time for those patients to receive an  (P <0.001) ( Table 4). An ARB/HCTZ diuretic combination was the most common combination therapy in the step-therapy group (n = 183, 14.1%) and in the comparison group (n = 1,590, 18.3%).

Addition of and Switch Rate to an ARB or ACEI
Of the 632 patients in the intervention group who attempted to obtain an ARB but received other antihypertensive therapy initially, 35.6%, 43.2%, and 51.1% were switched to or added an ARB within 3 months, 6 months, and 12 months, respectively (Table 5). Within 12 months, 25 of 104 (24.0%) intervention patients who applied for an ARB but were given ACEI monotherapy switched to or added an ARB. Of the 88 intervention patients who were given ACEI combination therapy when the ARB was denied, 33.0% (n = 29) switched to or added an ARB within 12 months. For the 5,462 intervention patients who were started initially on an ACEI, 6.1% (n = 333) switched to or added an ARB within 12 months (Table 5), similar to the 7.2% of 25,012 patients (n = 1,811) in the comparison group who started with ACEI therapy and later switched to or added an ARB within 12 months.

Effects of a Step-Therapy Program for Angiotensin Receptor Blockers on Antihypertensive Medication Utilitzation Patterns and Cost of Drug Therapy
Patient Characteristics and Initial Antihypertensive Therapy* ARB, and reduce average antihypertensive drug therapy costs. The rate of attempted initiation of ARB versus ACEI therapy was lower for the health plans with this intervention than for the comparison group without the step-therapy intervention for ARBs (19.2% vs. 25.8%, respectively).
The step-therapy program did shift patients to other antihypertensive therapy as evidenced by 48.8% of patients (n = 632) receiving an antihypertensive drug other than an ARB following the ARB claim rejection. About one third (192 of 632) of these patients received an ACEI alone or in some combination. The study also demonstrated that 6.6% of patients did not receive any antihypertensive therapy within 12 months of a rejected ARB claim. Furthermore, of the 1,296 patients who attempted to get ARB therapy, 578 (44.6%) received an ARB as initial therapy (via PA), but only as monotherapy in 233 patients. Over time, 323 patients who initially received other antihypertensive therapy switched to or added ARB therapy within 12 months, for a total of 901 patients (69.5%) who received an ARB within 12 months of the first attempt.
Our findings are similar to other studies that evaluate the impact of step-therapy programs. Compared with our cost savings of 13% per day of antihypertensive drug therapy, Dunn et al. found a 9% cost savings per day of antidepressant drug therapy associated with a step-therapy intervention for generic antidepressants, other than tricyclic antidepressants, before coverage of a brand-name antidepressant. 15 Analysis of a step-

Effects of a Step-Therapy Program for Angiotensin Receptor Blockers on Antihypertensive Medication Utilitzation Patterns and Cost of Drug Therapy
therapy program for COX-2 inhibitors suggested that up to 70% of patients did not attempt to obtain a PA after their claim for a COX-2 was rejected at the point of sale. 10 A step-therapy edit for proton pump inhibitors or nonsteroidal anti-inflammatory drugs found that 44% of patients received a different medication than was originally prescribed and 11% received no medication. 16 The 11% of patients who received no therapy is greater than the 6.6% of patients in our study who did not receive any antihypertensive therapy after the step-therapy claim rejection. Besides variations in patient demographics and other key factors, the methodologies used in assessing the percentage of patients not receiving any therapy after step edit differed. Our study evaluated medication use 12 months after the step edit via pharmacy claims while the proton pump inhibitor/nonsteroidal anti-inflammatory drug study by Cox et al. used a cross-sectional patient survey, without analysis of actual pharmacy claims, that included questions on why patients might not have received their medication. 16 While most patients continued with ACEI or other antihypertensive therapy following the rejected ARB attempt in the current study, the step-therapy program delayed the time for some patients to receive a (higher-cost) ARB, resulting in cost reduction for the 3 health plans where the step-therapy program was in place. Of the patients who received other antihypertensive therapy following the rejected ARB attempt, more than 50% switched to or added an ARB within 12 months.
The cost of therapy as measured by mean drug ingredient cost per patient was lower in the step-therapy group than in the overall comparison group, producing an unadjusted antihypertensive drug cost savings of $75.12 ($445.12 minus $370.00) per patient per year. Ordinary least squares regression analysis showed that the edit was associated with a $43.91 ingredient cost savings per patient over 12 months (Table 7). This difference in the descriptive savings of $75.12 per patient per year compared with $43.91 determined by regression analysis appears to be attributable to the "healthier" population in the intervention group that was younger and had a lower average severity of illness (CDS) score. This translates into approximately $298,000 in savings in 1 year, or $0.025 PMPM across the 1 million health plan members.
Although PA and step-therapy programs are generally effective at reducing direct drug costs, more research is needed on other outcomes, including medical use and costs and humanistic outcomes such as member and provider satisfaction. 5,11 This is the first study to examine the impact of a pharmacy step-therapy program for managing the use and costs of ARB therapy. The use of rejected and paid claims data in this analysis, compared with PA data only, allows for identification of cost savings associated with ARB claims avoided or delayed as a result of the step-therapy program. We identified those patients who encountered a rejected claim for an ARB and followed them for 12 months. While we do not know which patients attempted to get a PA or did not attempt to get a PA but were denied, we identified the antihypertensive therapy and associated costs in the 12-month follow-up period.

Limitations
First, while the study population was large, which provided adequate sample size to examine the distribution of patients as antihypertensive treatment changed over the follow-up period, the current study included only pharmacy claims data, so the effect of the step-therapy intervention on clinical outcomes such

Effects of a Step-Therapy Program for Angiotensin Receptor Blockers on Antihypertensive Medication Utilitzation Patterns and Cost of Drug Therapy
Step-Therapy Group  as blood pressure control and/or attainment of JNC 7 therapy goals is unknown. Second, we did not measure service outcomes that included member and provider satisfaction. Third, we were not able to assess why physician prescribing patterns were different between the intervention and comparison groups, and particularly why the prevalence of ACEI/ARB prescribing was nearly 3 times greater in the comparison group than in the intervention group. If this rate of prescribing ACEIs and ARBs is associated with some sort of "sentinel" effect, then the cost savings from this ARB step-therapy intervention are underestimated in the current study.

12-Month Antihypertensive Drug Utilization, Cost per Patient, and Cost per Day*
Fourth, while this was a "smart" step-therapy edit that did not simply reject the ARB claim and require the pharmacy provider to resolve the claim rejection, this intervention did result in 45% of affected patients receiving an ARB through PA. We did not measure the pharmacy and prescriber costs associated with requesting PA or changing drug therapy to an ARB alternative. We also did not assess administrative costs or the resources required to operate this intervention, and therefore could not calculate a return on investment from this managed care intervention. Other than program operation costs, some costs likely were incurred in physician office visits to switch or titrate therapy as well as pharmacy costs associated with explaining claim rejects to patients. Fifth, this study did not include the potential effects of rebate contracts on drug costs, which could offset some of the cost savings from the step-therapy intervention.
Our findings suggest that the step-therapy intervention for managing the use and cost of ARB therapy reduced the number of patients who were initially prescribed and received an ARB. However, we did identify patients who switched to or added an ARB within 12 months of the initial rejection in addition to those patients who were approved for ARB therapy at the time of application. While the drug cost savings were substantial from this step-therapy intervention, some of the savings would be consumed by program administrative costs and possible therapy interruption or disruption, including the 6.6% of patients who did not receive antihypertensive drug therapy after their initial ARB claims were rejected at the point of service.

nn Conclusions
A step-therapy intervention for ARBs (including ARB-HCTZ combinations) that required prior use of an ACEI or an ARB (including HCTZ combinations) was associated with an approximately 13% lower drug cost per day compared with a health plan with no step-therapy intervention. For the 3 health plans with this managed care intervention, the 1-year drug cost savings were about $368,000, or $0.03 PMPM across the approximately 1 million members. The administrative costs to implement and operate this ARB step-therapy intervention were estimated to be small but were not measured, and any costs that might be incurred in the form of either member or provider dissatisfaction or pharmacist and physician time were also not measured.

Unstandardized Standardized Variable
Definition Coefficients ($) Coefficients ($) P Value Step therapy Step therapy = Regression Analysis: Impact of ARB Step Therapy Yokoyama served as principal author of the study. Study concept and design were contributed by all authors. Data collection was the work of Yokoyama, with input from Yang; data interpretation was the work of all authors. Writing of the manuscript was the work of Yokoyama, with input from Preblick; its revision was the work of all authors.